Justification of Research in Humans

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Justification of Research in Humans

• Impossible to reach the important conclusions
  without studying humans
• Human physiologic studies, because
• animal responses often are not the same
• Epidemiological studies, because
• they depend on human susceptibilities
• and human interactions
• Agents for treating humans because
• animal experiments dont always predict
• results

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Justification (2)

• If youre going to treat humans, you must study
  humans
• Corollary If youre going to treat certain kinds
  of humans, then you must perform studies with
  them, for example
• Children, mentally impaired, ethnic groups,
  elderly, women, and pregnant women

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CONFLICTING PUBLIC HEALTH GOALS

• Protect the uninfected
• Protect the infected

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ETHICS

• The ethics of taking
• action vs. the ethics of avoiding action

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Definition of Ethics

• Ethics
• The discipline of dealing with what is good and
  bad, with moral duty and obligation
• A set of moral principles or values
• The principle of conduct governing an individual
  or group
• Websters Ninth New Collegiate Dictionary

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• History of the Ethical
• Research Movement

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The Nuremberg Code (World War II)

• Informed consent is absolutely essential
• Qualified researchers must use appropriate
  research designs
• There must be a favorable risk/ benefit ratio
• Participants must be free to stop at any time

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The Declaration of HelsinkiWorld Medical
Association(1964, 1975, 1983, 1989, 1996, 2002)

• The well-being of the subject should take
  precedence over the interests of science and
  society
• Consent should be in writing
• Use caution if participant is in dependent
  relationship with researcher
• Limited use of placebo, especially if treatment
  is available
• Greater access to benefit once research is
  concluded

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The Belmont Report (The U.S. National Commission
for the Protection of Human Subjects of
Biomedical and Behavioral Research, 1978)

• Ethical Principles and Guidelines for the
  Protection of Human Subjects of Research
• Respect for persons
• Beneficence
• Justice

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Council for International Organizations of
Medical Science (CIOMS) Guidelines 1993, 2002

• Nuremberg gt Helsinki gt CIOMS
• Informed consent
• Research in developing countries
• Protection of vulnerable populations
• Distribution of the burdens and benefits
• Role and responsibilities of ethics committees

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• Basic Concepts for
• Ethical Research

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• Basic Principles of Research on
• Human Subjects
• (The Belmont Report)
• Respect for persons
• Beneficence
• Justice

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Basic Principles of Research on Human Subjects (1)

• Respect for persons
• Choices of autonomous individuals should be
  respected
• People incapable of making their own choices
  should be protected
• Voluntary subjects need adequate information for
  decision-making

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Basic Principles of Research on Human Subjects (2)

• Beneficence
• Participation in research is associated with a
  favorable balance of potential benefits and harms
• Maximize possible benefits, minimize potential
  harm

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Basic Principles of Research on Human Subjects (3)

• Justice
• Participation in research is associated with a
  favorable balance of potential benefits and harms
• May not exploit or exclude vulnerable individuals
  who may benefit without good reason

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Summary - Principles and Foundations of Research
Ethics

• All codes and regulations advocate 3
• fundamental principles
• Respect for persons
• Beneficence
• Justice
• Research is a privilege, not a right
• The well-being of the participant is paramount

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• Assessment of Benefits and Risks

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Assure That Benefits Outweigh Risks

• Research must be justified on the basis of a
  favorable benefit/risk assessment for the
  research participant. Benefits must outweigh
  risks.
• This is similar to the principal of beneficence
  or do no harm. Researchers must protect
  participants from harm and maximize their
  well-being.

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Risk and Benefit Defined

• A risk refers to a harm or likelihood of a
  harm. The degree of severity of a possible harm
  may be unclear.
• A benefit refers to a positive value that
  accrues to the participant and/or to the society.
  The precise degree of gain that might accrue to
  the participant and/or to the society may be
  uncertain.

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Types of Risks and Benefits

• Risks or harms and benefits may be physical (pain
  or injury), psychological, social, economic, or
  legal.
• Risks or benefits of research may apply to
  individual participants, families, groups or
  organizations, communities, or nations.
• Risks and benefits to the research participant
  usually carry the most weight.

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General Principles

• There is absolutely no justification for inhumane
  treatment of participants.
• Risks to participants should always be reduced to
  the maximum extent possible.
• If a significant risk is involved, justification
  of the research must be examined with particular
  care.
• Whenever vulnerable persons are participants, the
  need to involve them must be carefully
  demonstrated.

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ETHICAL PROCEDURES FOR INTERNATIONAL RESEARCH
(U.S. PUBLIC HEALTH SERVICE)

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• FWAs
• Institutions that want to engage in research
  that do not have an IRB/IEC may submit a
  Federalwide Assurance form that designates one or
  more approved IRBs that are already registered
  with OHRP

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• IRB Authorization
• Reliance on another institution's IRB/IEC must
  be documented by a written agreement that is
  available for review by OHRP upon request. OHRP's
  sample IRB Authorization Agreement may be used
  for this purpose, or the institutions involved
  may develop their own agreement. Future
  designation of other IRB(s)/IEC(s) requires
  update of the FWA.

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• Foreign IRB Approval
• Following approval of the FWA by OHRP, the
  research project must be reviewed by the
  designated IRB/IEC and an approval letter issued
  listing the IRB number and the FWA number of the
  institution conducting the research, and signed
  by the IRB/IEC chair.

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• Multiple FWAs
• Funded projects may be required to get multiple
  FWAs if they "engage" other institutions or their
  employees as partners or participants in the
  project (see OHRP website for definition of
  "engagement"). Permitted use of other
  institutions' facilities does not constitute
  engagement.

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• Ethics Course Requirement
• All investigators (including non-U.S.
  investigators) must complete an approved ethics
  training course and obtain a certificate of
  completion (approved courses and completion
  certificates are available on the web) before
  their proposals can be approved by the IRB/IEC

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• RESEARCH IN POPULATIONS AND COMMUNITIES WITH
  LIMITED RESOURCES

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TWO RESPONSIBILITIES

• Prior to conducting research in a population or
  community with limited resources the
  researcher/sponsor should
• 1) Ensure the research responds to the health
  needs and priorities of the target community.
• 2) Ensure any product developed will be made
  available to the community.

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RESPONSIVENESS TO COMMUNITY HEALTH NEEDS

• It is not sufficient to determine disease
  prevalence and that new research is needed.
• If successful interventions result from the
  research they must be made available to the
  community.
• If this is not done, the research is
  exploitative.

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MAKING A PRIOR AGREEMENT

• Before the research begins, a plan should be
  offered in which the proposed product is made
  available to the host nation upon completion of
  the study.
• Participants should include representatives of
  the nations government, local authorities,
  community members, and NGO groups.

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COMPREHENSIVENESS OF THE AGREEMENT

• The agreement should include payments, royalties,
  distribution costs, subsidies, technology, and
  intellectual property.
• In some cases, international organizations,
  public and private, may also be included in the
  discussions.

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THE ETHICS OF CONDUCTING RESEARCH IN DEVELOPING
COUNTRIES

• When, if ever, should investigators use the
  standards of care/ethics of developing countries
  vs. developed countries (e.g., Tanzania drug
  trials)?
• Are investigators responsible for the health of
  their participants?
• Can participants in developing countries
  understand informed consent (e.g., is there an
  expectancy of benefit or treatment even if not
  stated in the informed consent)?
• Is it ethical to do research in developing
  countries on issues relevant to developed
  countries but not relevant to developing
  countries?

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REQUIREMENTS FOR COMMUNITY APPROVAL

• Community must have legitimate, empowered
  spokesperson(s)
• Community must have a common health-related
  culture
• A communication network for the community must be
  in place

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FACTORS INFLUENCING VOLUNTARY CONSENT

• Vulnerability to incentives
• Impact of community pressure
• Power of investigators to influence
• Ability of participants to understand goals and
  risks

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RESEARCH CONTROVERSIES IN DEVELOPING COUNTRIES

• Are placebo groups ethical?
• Should placebos reflect international or local
  standards of care?
• Should participants be assured care beyond the
  trials if so, for how long?
• Should care be provided to the trial community?
• Should trials be evaluated for scale-up
  feasibility before implementation?